Astrocyte growth is regulated by neuropeptides through Tis 8 and basic fibroblast growth factor.
The important intracellular mechanisms of astrocyte growth are not well defined. Using an inhibitor of astrocyte proliferation, atrial natriuretic peptide ( ANP), and the glial mitogen endothelin ( ET-3), we sought a common pathway for growth regulation in these neural cells. In cultured fetal rat diencephalic astrocytes, ANP selectively and rapidly inhibited the Tis 8 immediate early gene and protein. After 4 h, ANP selectively inhibited the basic fibroblast growth factor ( bFGF) gene and protein. ET-3 significantly stimulated both Tis 8 and bFGF mRNAs and protein, but also stimulated several other immediate early and growth factor/receptor genes. An antisense oligonucleotide to Tis 8 strongly prevented ET-stimulated thymidine incorporation, while the inhibitory action of ANP was enhanced. The Tis 8 antisense oligonucleotide also significantly reversed ET-stimulated bFGF transcription and enhanced the bFGF inhibition caused by ANP. In addition, an antisense oligonucleotide to bFGF significantly reversed the ET- stimulated thymidine incorporation and enhanced the ANP inhibition of DNA synthesis. The sequential modulation of Tis 8, followed by bFGF, provides a novel mechanism for both positive and negative regulation of astrocyte growth by endogenous neuropeptides.[1]References
- Astrocyte growth is regulated by neuropeptides through Tis 8 and basic fibroblast growth factor. Hu, R.M., Levin, E.R. J. Clin. Invest. (1994) [Pubmed]
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